rs12592307

Variant names:

• chr15-27845027-C-T
• rs12592307
• NM_000275.3:c.2364G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000275.3(OCA2):​c.2364G>A​(p.Ser788Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,506 control chromosomes in the GnomAD database, including 46,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4160 hom., cov: 32)
  • Exomes 𝑓: 0.22 (42014 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.606
• Publications: 25 publications found

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-27845027-C-T is Benign according to our data. Variant chr15-27845027-C-T is described in ClinVar as Benign. ClinVar VariationId is 255730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.606 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2364G>A	p.Ser788Ser	synonymous	Exon 23 of 24	NP_000266.2
	OCA2	NM_001300984.2		c.2292G>A	p.Ser764Ser	synonymous	Exon 22 of 23	NP_001287913.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2364G>A	p.Ser788Ser	synonymous	Exon 23 of 24	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.2292G>A	p.Ser764Ser	synonymous	Exon 22 of 23	ENSP00000261276.8
	OCA2	ENST00000910120.1		c.2610G>A	p.Ser870Ser	synonymous	Exon 25 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31785 AN: 151700 Hom.: 4157 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.277 AC: 69666 AN: 251336 AF XY: 0.274

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.564

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.223 AC: 325647 AN: 1460688 Hom.: 42014 Cov.: 33 AF XY: 0.225 AC XY: 163383 AN XY: 726708

African (AFR) AF: 0.101 AC: 3381 AN: 33470

American (AMR) AF: 0.435 AC: 19457 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8473 AN: 26124

East Asian (EAS) AF: 0.586 AC: 23266 AN: 39686

South Asian (SAS) AF: 0.312 AC: 26875 AN: 86206

European-Finnish (FIN) AF: 0.232 AC: 12367 AN: 53416

Middle Eastern (MID) AF: 0.267 AC: 1539 AN: 5766

European-Non Finnish (NFE) AF: 0.194 AC: 215820 AN: 1110956

Other (OTH) AF: 0.240 AC: 14469 AN: 60352

GnomAD4 genome AF: 0.209 AC: 31805 AN: 151818 Hom.: 4160 Cov.: 32 AF XY: 0.219 AC XY: 16240 AN XY: 74182

African (AFR) AF: 0.111 AC: 4576 AN: 41362

American (AMR) AF: 0.332 AC: 5066 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2901 AN: 5152

South Asian (SAS) AF: 0.311 AC: 1494 AN: 4804

European-Finnish (FIN) AF: 0.255 AC: 2677 AN: 10506

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13099 AN: 67942

Other (OTH) AF: 0.213 AC: 449 AN: 2110

Alfa AF: 0.203 Hom.: 5022

Bravo AF: 0.214

Asia WGS AF: 0.416 AC: 1446 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.209

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	2	Tyrosinase-positive oculocutaneous albinism (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.11
DANN	Benign	0.54
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12592307; hg19: chr15-28090173; COSMIC: COSV62341615;